Analyses on safety and efficacy of nonstandard dose of r-tPA in intravenous thrombolysis treated AIS patients

Abstract Background The widely recommended standard dose of recombinant tissue plasminogen activator(r-tPA) is 0.9mg/kg. Practically, the dose of r-tPA is still a topic that is constantly being discussed.Methods For this observational study, data were obtained from 537 patients who received r-tPA thrombolysis in Shanghai Sixth People’s Hospital stroke center in five years (2014-2019). Patients were divided into two groups: nonstandard dose group (0.6mg/kg ≤ dose < 0.9mg/kg) and standard dose group (0.9mg/kg). Different outcomes were observed: efficacy: 3 months mRS 0-1 (3m-mRS0-1); safety: symptomatic intracranial hemorrhage within 24 hours (24h-sICH) and 3 months mortality (3m-death). We also observed the effect of r-tPA dose coefficient on outcomes in different age and baseline National Institute of Health stroke scale (NIHSS) score subgroups. Results There are 265 patients given standard dose treatment, and 272 given nonstandard dose. There was no significant difference between non-standard dose group and standard dose group in 3m-mRS0-1, 3m-death and 24h-sICH (p=0.567, 0.327 and 0.415 respectively). The dose coefficient present a significant negative correlation (p=0.034, B=-4.290) with 3m-death in NIHSS <16 sub-group. Door to needle time (DNT) is the most important independent outcome-influential factor (MIOIF) in NIHSS ≥16 sub-group. The diabetes history and baseline NIHSS were the MIOIF in the age ≥80 year sub-group.Conclusions The non-standard dose group was as safe and effective as the standard dose group in our study. While, in NIHSS<16 group, lower doses seemed to be relative to 3m-death. Therefore, the standard dose should still be the first choice in r-tPA treated AIS patients.